Human chorionic gonadotropin and associated molecules

Abstract

When considering human chorionic gonadotropin (hCG) and hCG tests, it is important to realize that it is not a single biological molecule. The regular form of hCG produced by differentiated syncytotrophoblast cells (regular hCG) is a hormone made with the primary function of maintaining the myometrial and decidual spiral arteries and the vascular supply of the placenta during the full course of pregnancy. Hyperglycosylated hCG (hCG with double-size O-linked oligosaccharides) is made by undifferentiated cytotrophoblast cells. This is an autocrine hormone with separate functions, it maintains invasion as in implantation of pregnancy and malignancy in gestational trophoblastic diseases. A hyperglycosylated free β-subunit is produced by a high proportion of all malignancies. This functions as an autocrine hormone to promote the growth and invasion of the malignancy. It is important to realize when ordering an hCG test what you are measuring and whether the test ordered will detect appropriately these three variant of hCG as well as their degradation products. Most automated commercial laboratory tests, point-of-care test and over-the-counter tests are limited in what is detected, focusing only on regular hCG. This is in part due to the US FDA, who only consider hCG as a pregnancy test, and to whom only detection of regular hCG is critical. This may be a cause of test errors since primarily hyperglycosylated hCG is produced in early pregnancy, choriocarcinoma and germ cell testicular malignancies, and only free β-subunit may be produced in other germ cell malignancies (all applications for hCG test). The exceptions are the older style hCGβ radioimmunoassay and the Siemen’s Immulite platform hCG test which detect all variant and their degradation product appropriately. Regardless of test specificity limitations, assays for hCG variants are widely used clinically in pregnancy detection, early pregnancy detection, prediction of spontaneously aborting and ectopic pregnancies and prediction of trisomy pregnancies. hCG tests are essential in managing gestational trophoblastic diseases, whether hydatidiform mole, invasive mole or choriocarcinoma, and are very useful in management of testicular malignancies and other germ cell malignancies.